“Defects in meiosis lead to gametes with an incorrect number of chromosomes – this is one of the leading causes of miscarriage and birth defects”
Genome inheritance in sexually reproducing organisms requires the accurate formation of haploid gametes from diploid germ cells. This halving in chromosome number is achieved during meiosis, a specialized cell division program that involves the coordinated execution of the following chromosomal events: pairing of homologous chromosomes, the formation of inter-homologue crossover events during meiotic recombination, and the step-wise dissolution of sister chromatid cohesion during the two meiotic divisions. Defects in any of these processes result in the formation of aneuploid gametes, one of the leading causes of miscarriages and birth defects in humans.
The main goal of our research program is to understand the molecular mechanisms that ensure the proper execution and coordination of the different chromosomal events of the meiotic program. We are particularly interested in understanding how cohesin, the protein complex that mediates sister chromatid cohesion, and a group of HORMA-domain proteins that are also fundamental components of meiotic chromosomes, promote crossover formation and accurate chromosome segregation. To this end we are using C. elegans, a model organism especially well suited for the study of meiosis, and a combination of experimental approaches that includes genetics, biochemistry, proteomics, three-dimensional microscopy and live imaging of meiotic chromosomes.
Imaging of meiotic chromosomes using 3D super resolution microscopy. Axial elements are visualised by labelling of HORMA-domain protein HTP-3 (green), crossover sites are identified by foci of COSA-1 (red), while X chromosomes are labelled with anti-HIM-8 antibodies (blue). Using this approach, it is possible to trace individual chromosomes along their entire length (grey rods indicate paired X chromosomes).
Crawley, O., Barroso, C., Testori, S., Ferrandiz, N., Silva, N., Castellano-Pozo, M., Jaso-Tamame, A.L., and Enrique Martinez-Perez (2016). Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes. eLife, 5: e10851.
Gao J, Barroso C, Zhang P, Kim H-M. Li S, Labrador L, Lightfoot J, Gerashchenko M V, Labunskyy V M, Dong M-Q, Martinez-Perez E, and Colaiacovo M P (2016). N-terminal acetylation promotes synaptonemal complex assembly in C. elegans. Genes & Development, 30(21), 2404–2416.
Silva, N., Ferrandiz, N., Barroso, C., Tognetti, S., Lightfoot, J., Telecan, O., Encheva, V., Faull, P., Hanni, S., Furger, A., Snijders, A., Speck, C., and E. Martinez-Perez (2014). The Fidelity of Synaptonemal Complex Assembly Is Regulated by a Signaling Mechanism that Controls Early Meiotic Progression. Developmental Cell, 31(4), 503–511.
Labrador L., Barroso C., Lightfoot J., Müller-Reichert T., Flibotte S., Taylor J., Moerman D.G., Villeneuve A.M., Martinez-Perez E. (2013). Chromosome movements promoted by the mitochondrial protein SPD-3 are required for homology search during Caenorhabditis elegans meiosis. PLoS Genetics, 9 (5), e1003497.
Lightfoot, J., Testori, S., Barroso, C., & Martinez-Perez, E. (2011). Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and for the DNA damage checkpoint. Current Biology, 21, 1421-1430.